Coaggregation, cointernalization, and codesensitization of adenosine A(2A) receptors and dopamine D-2 receptors

Antagonistic and reciprocal interactions are known to exist between adenosine and dopamine receptors in the striatum. In the present study, double immunofluorescence experiments with confocal laser microscopy showed a high degree of colocalization of adenosine A A receptors (A(2A)R) and dopamine D-2 receptors (D2R) in cell membranes of SH-SY5Y human neuroblastoma cells stably transfected with human D2R and in cultured striatal cells. A(2A)R/D2R heteromeric complexes were demonstrated in coimmunoprecipitation experiments in membrane preparations from D2R-transfected SH-SY5Y cells and from mouse fibroblast Ltk(-) cells stably transfected with human D2R (long form) and transiently cotransfected with the A(2A)R double-tagged with hemagglutinin. Long term exposure to A(2A)R and D2R agonists in D2R-cotransfected SH-SY5Y cells resulted in coaggregation, cointernalization and codesensitization of A(2A)R and D2R. These results give a molecular basis for adenosine-dopamine antagonism at the membrane level and have implications for treatment of Parkinson's disease and schizophrenia, in which D2R are involved.